Salvinorin B methoxymethyl ether explained

Salvinorin B methoxymethyl ether (2-O-methoxymethylsalvinorin B) is a semi-synthetic analogue of the natural product salvinorin A used in scientific research.^{[1] [2]} It has a longer duration of action of around 2–3 hours, compared to less than 30 minutes for salvinorin A,^[3] and has increased affinity and potency at the κ-opioid receptor. It is prepared from salvinorin B.^[4] The crystal structure is almost superimposable with that of salvinorin A.^[5] Structures bound to the κ-opioid receptor have also been reported.^[6]

Salvinorin B methoxymethyl ether has a K_i of 0.60 nM at the κ opioid receptor,^[7] and is around five times more potent than salvinorin A in animal studies, although it is still only half as potent as its ethoxymethyl ether homolog, 'symmetry'.^{[8] [9]}

See also

• RB-64

Notes and References

1. Inan S, Lee DY, Liu-Chen LY, Cowan A . Comparison of the diuretic effects of chemically diverse kappa opioid agonists in rats: nalfurafine, U50,488H, and salvinorin A . Naunyn-Schmiedeberg's Archives of Pharmacology . 379 . 3 . 263–270 . March 2009 . 18925386 . 10.1007/s00210-008-0358-8 . 8123431 .
2. McLennan GP, Kiss A, Miyatake M, Belcheva MM, Chambers KT, Pozek JJ, Mohabbat Y, Moyer RA, Bohn LM, Coscia CJ . 6 . Kappa opioids promote the proliferation of astrocytes via Gbetagamma and beta-arrestin 2-dependent MAPK-mediated pathways . Journal of Neurochemistry . 107 . 6 . 1753–1765 . December 2008 . 19014370 . 2606093 . 10.1111/j.1471-4159.2008.05745.x .
3. Wang Y, Chen Y, Xu W, Lee DY, Ma Z, Rawls SM, Cowan A, Liu-Chen LY . 6 . 2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A . The Journal of Pharmacology and Experimental Therapeutics . 324 . 3 . 1073–1083 . March 2008 . 18089845 . 2519046 . 10.1124/jpet.107.132142 .
4. Lee DY, Karnati VV, He M, Liu-Chen LY, Kondaveti L, Ma Z, Wang Y, Chen Y, Beguin C, Carlezon WA, Cohen B . 6 . Synthesis and in vitro pharmacological studies of new C(2) modified salvinorin A analogues . Bioorganic & Medicinal Chemistry Letters . 15 . 16 . 3744–3747 . August 2005 . 15993589 . 10.1016/j.bmcl.2005.05.048 .
5. Munro TA, Ho DM, Cohen BM . 2012 . Salvinorin B methoxymethyl ether . Acta Crystallographica Section E . 68 . 11 . o3225–o3226 . 10.1107/s1600536812043449 . 3515309 . 23284529. 2012AcCrE..68O3225M .
6. Han J, Zhang J, Nazarova AL, Bernhard SM, Krumm BE, Zhao L, Lam JH, Rangari VA, Majumdar S, Nichols DE, Katritch V, Yuan P, Fay JF, Che T . 6 . Ligand and G-protein selectivity in the κ-opioid receptor . Nature . 617 . 7960 . 417–425 . May 2023 . 37138078 . 10172140 . 10.1038/s41586-023-06030-7 . 2023Natur.617..417H .
7. Munro TA, Duncan KK, Xu W, Wang Y, Liu-Chen LY, Carlezon WA, Cohen BM, Béguin C . 6 . Standard protecting groups create potent and selective kappa opioids: salvinorin B alkoxymethyl ethers . Bioorganic & Medicinal Chemistry . 16 . 3 . 1279–1286 . February 2008 . 17981041 . 2568987 . 10.1016/j.bmc.2007.10.067 .
8. Baker LE, Panos JJ, Killinger BA, Peet MM, Bell LM, Haliw LA, Walker SL . Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats . Psychopharmacology . 203 . 2 . 203–211 . April 2009 . 19153716 . 10.1007/s00213-008-1458-3 . free .
9. Mercury D, Feelodd D . 2008 . First look at a new psychoactive drug: symmetry (salvinorin B ethoxymethyl ether) . Entheogen Review . 16 . 4 . 136–145 . 1066-1913 .